Tylleskar Ida, Skulberg Arne Kristian, Nilsen Turid, Skarra Sissel, Dale Ola
Tidsskr Nor Laegeforen. 2019 Sep 23;139(13). doi: 10.4045/tidsskr.19.0162. Print 2019 Sep 24.
Bystander administration with naloxone nasal spray can prevent deaths from opioid overdose. To achieve optimal nasal absorption of naloxone, the spray must be administered at low volume with high concentration of the drug. The study aimed to investigate the bioavailability and absorption pattern for a new naloxone nasal spray.
In an open, randomised, two-way crossover study undertaken in five healthy men, naloxone 2 mg (20 mg/ml) in nasal spray was compared with 1 mg intravenously administered naloxone. A total of 15 blood samples were taken over a period of six hours after administration. The drug concentration was determined using liquid chromatography tandem-mass spectrometry. Pharmacokinetic variables were calculated using non-compartmental analysis.
Bioavailability for intranasal naloxone was 47 % (minimum-maximum values 24-66 %). Maximum concentration (Cmax) was 4.2 (1.5-7.1) ng/ml, and this was achieved (Tmax ) after 16 (5-25) minutes.
The nasal spray resulted in a rapid systemic absorption with higher serum concentrations than intravenous naloxone 10-240 minutes after intake. The pilot study indicated that the highly concentrated nasal spray may provide a therapeutic dose of naloxone with a single spray actuation. The findings led to further commercial development of the medication.
旁观者使用纳洛酮鼻喷雾剂可预防阿片类药物过量致死。为实现纳洛酮的最佳鼻腔吸收，喷雾剂必须以低容量、高浓度药物进行给药。本研究旨在调查一种新型纳洛酮鼻喷雾剂的生物利用度和吸收模式。
在一项针对五名健康男性进行的开放、随机、双向交叉研究中，将2毫克（20毫克/毫升）的纳洛酮鼻喷雾剂与静脉注射1毫克纳洛酮进行比较。给药后6小时内共采集15份血样。使用液相色谱串联质谱法测定药物浓度。采用非房室分析计算药代动力学变量。
鼻内纳洛酮的生物利用度为47%（最小值 - 最大值为24 - 66%）。最大浓度（Cmax）为4.2（1.5 - 7.1）纳克/毫升，在16（5 - 25）分钟后达到该浓度（Tmax）。
鼻喷雾剂导致快速的全身吸收，摄入后10 - 240分钟时血清浓度高于静脉注射纳洛酮。初步研究表明，高浓度鼻喷雾剂单次喷雾启动可能提供治疗剂量的纳洛酮。这些发现促使该药物进一步进行商业开发。
